Human cancer has become the leading cause of death for Americans under the age of 85. Although the overall cancer death rate has declined, approximately 470,000 people died of cancer in 2002. Lung cancer has the highest mortality rate of human cancers; prostate, ovarian, colon and breast cancers are also major causes of cancers for men and women. Although the five year survival rate has risen to 74 percent, 570,260 people are expected to die of cancer in 2005. Preventing and curing human cancer poses a challenge because many of the precursors to the disease are unknown. In many cancers, such as ovarian cancer, late diagnosis of the disease dramatically decreases survival rates. Chemotherapy is the primary treatment for cancers that have metastasized but it too poses problems. While in some cancers chemotherapy can prevent the spreading of the disease, slow cancer cell growth, and even cure the cancer, studies have shown that many types of cancer cells can develop resistance to chemotherapy drugs, causing a recurrence of the cancer and a higher mortality rate. Cancer prevention (chemoprevention) is another way to prevent human cancer. Although the mechanism(s) involved in the progression of human cancer are still unclear, increasing evidence in cancer prevention literature points toward the role of autocrine and paracrine factors in the development of cancer tumorigenesis and angiogenesis. Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) play an important role in cancer development.
Apigenin is a nontoxic dietary flavonoid that has been used as a food supplement and antioxidant. Our study shows that apigenin can specifically inhibit several human cancer cell proliferation, decrease tumor growth and angiogenesis in vivo. Apigenin did not induce apoptosis of normal human cells at up to 40 μM apigenin. We also showed that apigenin inhibited VEGF expression which is required for tumor initiation and development. These data demonstrate that apigenin can be used for cancer prevention to inhibit the tumor initiation and development, and to inhibit human cancers.
Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and growth. Angiogenesis is the formation of new blood vessels from pre-existing ones and is required for tumor growth and metastasis. Inhibiting the role of VEGF in promoting angiogenesis and tumor growth is a good target for cancer therapy. HIF-1 is overexpressed in many types of human cancers and it regulates VEGF expression at the transcriptional level. Therefore, inhibition of HIF-1 can potentially play a role in inhibiting angiogenesis and tumor growth.
Most caner patients especially in advanced disease stages require chemotherapy. Chemotherapy regime has proven to improve disease-free and overall survival in cancer patients. However, chemotherapeutic drugs can cause many side effects, including myelosuppression, immunosuppression, hepatotoxicity, nausea and vomiting, sore mouth, and diarrhea. The side effects can be very severe that interrupt the therapy or can even cause death. Several studies suggest that dietary supplementation with antioxidants can influence the response to chemotherapy as well as the development of adverse side effects that results from treatment with antineoplastic agents. Our studies show that, in addition to the antiangiogenic effects, apigenin synergizes with many chemotherapeutic drugs in inhibiting cancer cell growth. We propose that coadministration of apigenin may be of benefit for cancer treatment by reducing the doses of conventional chemotherapeutic reagents and thereby alleviates the side effects of chemotherapy, and apigenin treatment also confer the drug resistant tumors or cancer cells to be sensible to the same drug again.